Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM. CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study.

Exposure to asbestos results in serious risk of developing lung and mesothelial diseases. Currently, there are no biomarkers that can be used to diagnose asbestos exposure. The purpose of the present study was to determine whether the levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum are elevated in persons exposed to asbestos. The primary study group consisted of 76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly exposed to asbestos. The secondary study group consisted of 535 subjects possibly exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All study subjects who were possibly exposed to asbestos had a certificate of asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare. For the primary study group, levels of serum CCL3 did not differ between the two groups. However, the detection rate of CCL3 in the serum of healthy subjects possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis, and lung cancer groups had serum CCL3 levels and detection rates similar to that of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three of the patients with malignant mesothelioma had exceptionally high CCL3 levels. Malignant mesothelioma cells from four biopsy cases and an autopsy case were positive for CCL3, possibly identifying the source of the CCL3 in the three malignant mesothelioma patients with exceptionally high serum CCL3 levels. In conclusion, a significantly higher percentage of healthy persons possibly exposed to asbestos had detectable levels of serum CCL3 compared to healthy unexposed control subjects.

[A case of lung infection due to Mycobacterium abscessus (M. abscessus) complicated with primary macroamylasemia].

We report a case of lung infection due to Mycobacterium abscessus (M. abscessus), complicated with primary macroamylasemia. A 76-year-old man was admitted to our hospital in August 2002 because of bloody sputum and an abnormal shadow found on chest radiography. The patient had had pulmonary tuberculosis from 1998 to 2000. He was found to be antacid bacillus-positive (Gaffky 5) on examination of the sputum in August 2002, but after hospitalization was negative for tuberculosis bacillus on sputum examination by the PCR method. We had suspected the presence of non-tuberculous mycobacterial disease since the patient's admission, and had started a regime of three drugs: clarithromycin, rifampicin, and ethambutol. The bacteria were identified as M. abscessus in a later sputum culture examination. It was noticed that the blood amylase level was high, and the disease was diagnosed as primary macroamylasemia. Such a case of lung infection due to M. abscessus complicated with macroamylasemia has rarely been reported in Japan.

[A case of child obesity hypoventilation syndrome (OHS) improved by bi-level positive airway pressure (BiPAP)].

A 5-year-old boy was admitted to our hospital because of severe obesity and disordered breathing with snoring during sleep. Child OHS was diagnosed using polysomnography (PSG). Although he was treated initially with nasal CPAP, it was not acceptable to him. BiPAP produced marked reduction of the respiratory disorders during sleep, as confirmed by PSG. Few reports of BiPAP for child OHS have appeared in Japan. We concluded that child OHS could be successfully treated with BiPAP when nasal CPAP was not acceptable.

[Longitudinal assessment of IFN-gamma production in patients with pulmonary tuberculosis complicated with diabetes mellitus].

Patients with diabetes mellitus (DM) are more susceptible to bacterial infection including pulmonary tuberculosis. To define the immunopathologic mechanisms underlying pulmonary tuberculosis in patients with DM, the production of IFN-gamma by CD4+ T cells or PBMC were followed up longitudinally during antituberculous chemotherapy. At the time of diagnosis, IFN-gamma production by CD4+ T cells in either tuberculosis patients without DM (TB) or with DM was significantly lower than that in the healthy control. CD4+ T cells in tuberculosis patients with DM under poor control (DM(p)TB) produced significantly less IFN-gamma than did patients with DM under good control (DM(g)TB). In longitudinal studies, IFN-gamma production in both TB and DM(g)TB patients returned to the control level by 6 months, whereas the production in DM(p)TB patients remained depressed. There was no significant relation between regimens of antituberculous chemotherapy and the production of IFN-gamma by PBMC in all subject groups. IFN-gamma production was depressed in DM(p)TB patients treated with HREZ for 6 months. These results indicate that depressed production of IFN-gamma in DM(p)TB patients is prolonged not due to tuberculous infection but intrinsic defect presumably induced by poorly controlled DM.